Long-range Goal: The project will lay foundation for future applications of a new and powerful functional imaging techniques for the detection and study of retinal dysfunction in man. The proposed studies will contribute significantly to establishing the connection between components of the ERG response in man and retinal mechanisms known from electrophysiological studies in animal models. During the previous project period the concept of functional imaging by means of multi-input nonlinear system analysis has been successfully tested in several projects and numerous pilot studies. A new methodology of source identification has evolved that will now be used to isolate and characterize signal components, particularly those from the inner retina. Nonlinearities in retinal processing which are primarily due to adaptive mechanisms will be used to discriminate signal sources. Their topographic distribution will then be compared with known anatomical properties for identification of the sources. The project will resolve standing controversies surrounding the pattern ERG and the oscillatory potentials and pave the way to early detection and characterization of glaucomatous damage. Specific aims are: 1. Discrimination of ERG components from pre- and post-receptoral mechanisms in the photopic ERG. Determination of the dynamics of post- receptoral adaptation. 2. Identification of ERG components from the proximal retina by means of the topographic distribution of their nonlinear characteristics. Study of pathological changes of these components in glaucoma patients. 3. Localization and characterization of slow adaptive mechanisms that are observed at mesopic levels and appear to be rod mediated. 4. Test of the hypothesis that changes in proximal components of the ERG (particularly latency increases in the pattern electroretinogram and the oscillatory potentials) toward the center are attributable to adaptation pooling. 5. Analysis of spatial extent and dynamics of long-rang spatial adaptation.